Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis

Abstract Osteosarcoma is the most common type of primary malignant tumor of the bone, with a high metastatic rate and poor prognosis. Therefore, it is important to further elucidate the molecular mechanisms involved in the development of osteosarcoma and explore new molecular therapeutic targets. Long intergenic nonprotein-coding RNA 707 (LINC00707) is an oncogenic gene in several cancers. In this study, we further clarified its role and regulatory mechanism in osteosarcoma. We found that LINC00707 levels are significantly higher in the osteosarcoma cell lines SW 1353, HOS, U-2 OS, MG-63, and Saos-2 compared to those in human fetal osteoblastic cell line hFOB1.19. LINC00707 silencing suppressed cell proliferation, migration, and invasion of MG-63 and Saos-2 cells. Moreover, LINC00707 can act as a competitive endogenous RNA of miR-338-3p, and miR-338-3p inhibitor and AHSA1 overexpression alleviated the effect of LINC00707 silencing. In conclusion, we demonstrated high expression of LINC00707 in osteosarcoma cell lines and that silencing LINC00707 suppresses cell proliferation, migration, and invasion by targeting the miR-338-3p/AHSA1 axis in MG-63 and Saos-2 cells. These findings suggest that LINC00707 may serve as a potential target for osteosarcoma treatment.

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Sex Determining Region Y-Box 12 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Activating β-Catenin/T Cell Factor Axis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2783 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2225-2231

Author(s):

Minhua Lu ◽

Xingguang Chen

Keyword(s):

Cell Lines ◽

Critical Role ◽

Migration And Invasion ◽

Osteoblastic Cell ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Western Blot Assay ◽

Osteoblastic Cell Line ◽

Well Assay ◽

And Migration

Objectives: This study aims to clarify the role of sex determining region Y-box 12 (SOX12) in accelerating the proliferative, migratory and invasive abilities of osteosarcoma (OS) via β-catenin/TCF axis. Materials and Methods: SOX12 levels in human osteosarcoma cell lines and human fetal osteoblastic cell line were determined by RT-qPCR. The proliferation rates of osteosarcoma cells were both determined by CCK-8 assay and EdU staining. In addition, osteosarcoma cell migration and migration were determined by wound healing assay and trans-well assay, respectively. TOPFlash/FOPFlash reporter activity assay and western blot assay were simultaneously performed for the detection of β-catenin/TCF axis. Results: SOX12 was elevated in osteosarcoma cell lines, developing the critical role in proliferation, migration and invasion of osteosarcoma cells. The β-catenin/TCF pathway was activated in osteosarcoma. SOX12 overexpression exerted promotive effects on activation of β-catenin/TCF pathway and SOX12 knockdown showed the opposite effects. Conclusions: SOX12 accelerates proliferation, migration and invasion of osteosarcoma cells by activating β-catenin/TCF axis, thus stimulating the progression of OS.

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Identifying the Molecular Cause of Extreme Endoplasmic Reticulum Dilation in Pediatric Osteosarcoma and Its Relationship to the Disease

10.21007/etd.cghs.2021.0555 ◽

2021 ◽

Author(s):

◽

Rachael Wood ◽

Keyword(s):

Endoplasmic Reticulum ◽

Genomic Instability ◽

Cell Lines ◽

Molecular Signature ◽

Osteosarcoma Cell ◽

Copii Vesicle ◽

Molecular Therapeutic ◽

Molecular Therapeutic Targets ◽

Pediatric Osteosarcoma ◽

Crispr Activation

Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology to normal.

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MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R

Cellular Physiology and Biochemistry ◽

10.1159/000438653 ◽

2016 ◽

Vol 38 (2) ◽

pp. 598-608 ◽

Cited By ~ 32

Author(s):

Guangnan Chen ◽

Tingting Fang ◽

Zhongming Huang ◽

Yiying Qi ◽

Shaohua Du ◽

...

Keyword(s):

Cell Line ◽

Cell Lines ◽

Luciferase Reporter ◽

Osteoblastic Cell ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Invasion And Metastasis ◽

Osteoblastic Cell Line ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cell

Background/Aims: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. Methods: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR). The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. Results: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. Conclusion: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.

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SOX10 induces epithelial–mesenchymal transition and contributes to nasopharyngeal carcinoma progression

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0160 ◽

2018 ◽

Vol 96 (3) ◽

pp. 326-331 ◽

Cited By ~ 4

Author(s):

Ping He ◽

Xiaojie Jin

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Mesenchymal Transition

Objective: The aim of this study was to investigate the role of SOX10 in nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. Methods: The expression of SOX10 was initially assessed in human NPC tissues and a series of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot. Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell migration and invasion assays, respectively. Finally, nude mice tumorigenicity experiments were performed to evaluate the effects of SOX10 on NPC growth and metastasis in vivo. Results: SOX10 was significantly increased in NPC tissues and cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited cell proliferation, migration, and invasiveness, as well as the epithelial–mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further demonstrated that disrupted SOX10 expression restrained NPC growth and metastasis, especially in lung and liver. Conclusion: Taken together, our data confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential therapeutic target against this disease.

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Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA

Journal of Oncology ◽

10.1155/2010/530745 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 30

Author(s):

Conor C. Lynch ◽

Tracy Vargo-Gogola ◽

Lynn M. Matrisian ◽

Barbara Fingleton

Keyword(s):

Cell Proliferation ◽

Cell Migration ◽

Epithelial Cell ◽

Cell Lines ◽

Molecular Mechanisms ◽

Cellular Proliferation ◽

Migration And Invasion ◽

Cell Contact ◽

E Cadherin ◽

Cell Cell

Perturbations in cell-cell contact machinery occur frequently in epithelial cancers and result in increased cancer cell migration and invasion. Previously, we demonstrated that MMP-7, a protease implicated in mammary and intestinal tumor growth, can process the adherens junction component E-cadherin. This observation leads us to test whether MMP-7 processing of E-cadherin could directly impact cell proliferation in nontransformed epithelial cell lines (MDCK and C57MG). Our goal was to investigate the possibility that MMP-7 produced by cancer cells may have effects on adjacent normal epithelium. Here, we show that MMP-7 processing of E-cadherin mediates, (1) loss of cell-cell contact, (2) increased cell migration, (3) a loss of epithelial cell polarization and (4) increased cell proliferation via RhoA activation. These data demonstrate that MMP-7 promotes epithelial cell proliferation via the processing of E-cadherin and provide insights into the molecular mechanisms that govern epithelial cell growth.

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LncRNA EBLN3P promotes the progression of osteosarcoma through modifying the miR-224-5p/Rab10 signaling axis

Scientific Reports ◽

10.1038/s41598-021-81641-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shuhong Dai ◽

Ning Li ◽

Ming Zhou ◽

Yue Yuan ◽

Ding Yue ◽

...

Keyword(s):

Cell Proliferation ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Cell Counting ◽

Luciferase Assay ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Regulatory Loop

AbstractThe treatment of patients with advanced-stage osteosarcoma represents a major challenge, with very few treatments currently approved. Although accumulating evidence has demonstrated the importance of lncRNAs in osteosarcoma, the current knowledge on the functional roles and molecular mechanisms of lncRNA endogenous born avirus-like nucleoprotein (EBLN3P) is limited. At present, the expressions of EBLN3P and miR-224-5p in osteosarcoma tissues were quantified by reverse transcription-quantitative PCR assay, and the expression of Ras-related protein 10 (Rab10) in osteosarcoma tissues was quantified by immunohistochemistry and western-blotting. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P, Rab10 and miR-224-5p. The regulatory role of EBLN3P or miR-224-5p on cell proliferation, migration and invasion ability were verified by Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interaction among EBLN3P, miR-224-5p and Rab10 were testified by luciferase. The increased expression of EBLN3P and Rab10 and decreased expression of miR-224-5p were observed in osteosarcoma tissues and cell lines. Besides, the overexpression of EBLN3P or knockdown of miR-224-5p were revealed to promote the proliferation, migration and invasion of osteosarcoma cells. Bioinformatics analysis and luciferase assay revealed that EBLN3P could directly interacted with miR-224-5p to attenuate miR-224-5p binding to the Rab10 3′-untranslated region. Furthermore, the mechanistic investigations revealed activation of the miR-224-5p/Rab10 regulatory loop by knockdown of miR‐372-3p or overexpression of Rab10, thereby confirming the in vitro role of EBLN3P in promoting osteosarcoma cell proliferation, migration and invasion. To the best of our knowledge, the present study is the first to demonstrate that EBLN3P may act as a competitive endogenous RNA to modulate Rab10 expression by competitive sponging to miR-224-5p, leading to the regulation of osteosarcoma progression, which indicates a possible new approach to osteosarcoma diagnosis and treatment.

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LncRNA RBM5-AS1 Promotes Osteosarcoma Cell Proliferation, Migration, and Invasion

BioMed Research International ◽

10.1155/2021/5271291 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Biyong Deng ◽

Runsang Pan ◽

Xin Ou ◽

Taizhe Wang ◽

Weiguo Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Western Blotting ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Pediatric Age Group ◽

The Relationship

Purpose. Osteosarcoma (Os) is the most frequent malignant tumor of the bone in the pediatric age group, and accumulating evidences show that lncRNAs play a key role in the development of Os. Thus, we investigated the role of RBM5-AS1 and its molecular mechanism. Methods. The expression of RBM5-AS1 in Os tissues and cell lines was detected by real-time polymerase chain reaction (QPCR). The effect of RBM5-AS1 on the proliferation of Os cells was detected using CCK8 assays and flow cytometry. The effect of RBM5-AS1 on the migration and invasion of Os cells was detected by transwell assays. And we performed QPCR and western blotting assays to investigate the relationship between RBM5-AS1 and RBM5. Finally, western blotting assays were performed to explore the mechanism of RBM5. Results. LncRNA RBM5-AS1 was overexpressed in the Os tissues and cell lines. And lncRNA RBM5-AS1 promoted Os cell proliferation, migration, and invasion in vitro and tumor growth in vivo. LncRNA RBM5-AS1 targets RBM5 in Os cells. Conclusion. To sum up, the results showed that lncRNA RBM5-AS1 promotes cell proliferation, migration, and invasion in Os.

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The proliferation and invasion of osteosarcoma are inhibited by miR-101 via targetting ZEB2

Bioscience Reports ◽

10.1042/bsr20181283 ◽

2019 ◽

Vol 39 (2) ◽

Cited By ~ 5

Author(s):

Haopeng Lin ◽

Xiaodong Zheng ◽

Ting Lu ◽

Yang Gu ◽

Canhao Zheng ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Molecular Mechanisms ◽

Bone Cell ◽

Luciferase Reporter ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Direct Target ◽

Proliferation And Invasion

AbstractHaving a better grasp of the molecular mechanisms underlying carcinogenesis and progression in osteosarcoma would be helpful to find novel therapeutic targets. Different types of cancers have presented abnormal expression of miRNA-101 (miR-101). Nevertheless, we still could not figure out what expression of miR-101 in human osteosarcoma is and its biological function. Thus, we conducted the present study to identify its expression, function, and molecular mechanism in osteosarcoma. We detected the expression of miR-101 in osteosarcoma samples and cell lines. The effects of miR-101 on osteosarcoma cells’ proliferation and invasion were evaluated. Luciferase reporter assay was applied to identify the direct target of miR-101. Compared with adjacent normal specimens and normal bone cell line by using qPCR, the expression levels of miR-101 in osteosarcoma specimens and human osteosarcoma cell lines distinctly decreased. According to function assays, we found that overexpression of miR-101 significantly inhibited the cell proliferation and invasion in osteosarcoma cells. Moreover, we confirmed that zinc finger E-box binding homeobox 2 (ZEB2) was a direct target of miR-101. In addition, overexpression of ZEB2 could rescue the inhibition effect of proliferation and invasion induced by miR-101 in osteosarcoma cells. MiR-101 has been proved to be down-regulated in osteosarcoma and has the ability to suppress osteosarcoma cell proliferation and invasion by directly targetting ZEB2.

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MiR-125b Functions as a Tumor Suppressor and Enhances Chemosensitivity to Cisplatin in Osteosarcoma

Technology in Cancer Research & Treatment ◽

10.1177/1533034615618849 ◽

2016 ◽

Vol 15 (6) ◽

pp. NP105-NP112 ◽

Cited By ~ 23

Author(s):

Fei Wang ◽

Dapeng Yu ◽

Zhen Liu ◽

Ruijie Wang ◽

Yan Xu ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Suppressor ◽

Cell Lines ◽

Noncoding Rna ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Human Osteosarcoma ◽

Translational Level

MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. To date, the potential microRNAs regulating the growth and progression of osteosarcoma are not fully identified yet. Previous reports have shown differentially expressed miR-125b in osteosarcoma. However, the role of miR-125b in human osteosarcoma has not been totally illuminated. In this study, we have shown that miR-125b was downregulated in human osteosarcoma tissues compared to the adjacent tissues and effects as a tumor suppressor in vitro. We found that stable overexpression of miR-125b in osteosarcoma cell lines U2OS and MG-63 inhibited cell proliferation, migration, and invasion. Our data also verified that Bcl-2 is the target of miR-125b. Meanwhile, we showed that Bcl-2 was inversely correlated with miR-125b in osteosarcoma tissues. More importantly, we proved that miR-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting Bcl-2. In conclusion, our data demonstrate that miR-125b is a tumor suppressor and support its potential application for the treatment of osteosarcoma in the future.

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MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Cellular Physiology and Biochemistry ◽

10.1159/000430237 ◽

2015 ◽

Vol 37 (3) ◽

pp. 1123-1133 ◽

Cited By ~ 41

Author(s):

Wenbo Zhang ◽

Chen Zou ◽

Lei Pan ◽

Ying Xu ◽

Weidong Qi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Lines ◽

Molecular Mechanisms ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Integrated Analysis ◽

Loss Of Function ◽

Invasion And Migration ◽

Tumorigenesis And Progression

Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

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